Tuesday, May 02, 2017

MHRA Yell "Barracuda!"

I think I am familiar with the fact that you are going to ignore this particular problem until it swims up and bites you on the ass! ~ Matt Hooper - Jaws

The above photo and caption are from the movie Jaws. Power and money-hungry Mayor Larry Vaughn, played by Murray Hamilton, refuses to acknowledge that the residents of Amity are at risk of a shark attack. If Vaughn doesn't close the beaches, the shark could harm and kill citizens. Matt Hooper, played by Richard Dreyfuss, is an oceanographer with a special interest in the study of sharks. He uses his knowledge to try and convince Vaughn to protect the town, but Vaughn ignores him. Given the popularity of Jaws (it won an Oscar), I assume we all know the outcome of Vaughn's callous ignorance, right?

I'm not Matt Hooper, but lately, I feel like him. For years I've been at loggerheads with the MHRA as I seek answers to improve public health. Today's blog spotlights my latest correspondence to/from the MHRA about the increased risk of adult suicide posed by Paxil.

The MHRA and FDA know SSRIs are not recommended for consumers under the age of 24 because these products increase the suicide risk. In the US there is a black box warning, and in Europe, the patient information leaflet highlights this increased risk of suicide for any consumers under age 24. It is actually printed in bold face font. (See Doublespeak)

What we don't know is how and why regulatory authorities chose to highlight the product's dangers in consumers under 24 and not communicate the increased suicide risk for consumers over 24.

Let's look at the facts regarding Paxil clinical trials. (Paxil is known as Seroxat in Europe.)

In GSK's Paxil pediatric trials, which included more than 1,000 patients treated with Paxil, there were zero completed suicides. We know this because GSK's vice president for regulatory affairs, Dr. David Wheadon, admitted this in a written statement. What we don't know is how many of the children who were given Paxil developed suicidal thoughts and actions. MHRA and the FDA apparently feel this information is not important for the public's viewing.

In GSK's Paxil adult trials, we know 22 deaths occurred, 80% of which were people over age 30. (See here.) What we now know, thanks to the evidence made public in the Dolin vs. GSK trial, 42 people taking Paxil developed suicidal thoughts and actions.(See here)

So, to sum up: No deaths occurred in Paxil pediatric trials, and 22 deaths occurred in Paxil adult trials. Twenty of these deaths were completed suicides, and 80% of these were people over age 30.

Surely, the MHRA never had this information?

Wrong.

Here's a series of emails between myself and the MHRA. Spelling and grammatical errors from the MHRA are as received.

On the current Seroxat Patient Information leaflet (Revised 11/01/2017) it states, under the subheading "Thoughts of suicide and worsening of your depression or anxiety disorder"...

If you are depressed and/or have anxiety disorders you can sometimes have thoughts of harming or killing yourself. These may be increased when first starting antidepressants, since these medicines all take time to work, usually about two weeks but sometimes longer.

You may be more likely to think like this:

· If you have previously had thoughts about killing or
harming yourself.
· If you are a young adult. Information from clinical
trials has shown an increased risk of suicidal
behaviour in adults aged less than 25 years with
psychiatric conditions who were treated with an
antidepressant.

Q: Could you please explain why "young adult" is in boldface type font and who made the decision to include "young adult" in a boldface type font?

A meta‑analysis of placebo‑controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old (see also section 5.1).

As the above suggests that this particular age group are most at risk, the MAH will have suggested the emboldening of the text within the PIL. There are fors and againsts the use of emboldening, but in this particular case it has been considered appropriate.

Plaintiff’s Exhibit 347: Each picture depicts a real person who completed suicide while taking Paxil in a GSK-clinical trial. The red “Vs” mean their specific suicides were violent in nature. There were multiple suicides using firearms, including a murder suicide by one patient. There were also two deaths from people jumping in front of trains.When it comes to suicide attempts, GSK did not keep track of all the attempted suicides in their clinical trials because, according to their company witness, it would be too burdensome.

For clarification. Were the MHRA notified of the 22 deaths that occurred in paroxetine (Seroxat) clinical trials carried out by GSK (SmithKline Beecham) and that 16 of those deaths (80%) were attributed to adults over the age of 30?

As stated in the previous email from Chris Penny the MHRA is informed of serious adverse reactions occurring in clinical trials in compliance with current legislation.

The deaths that you are referring to took place between approximately 1983 and 2003. This data would have been submitted to European Competent Authorities and the suicidality risk of paroxetine was formally addressed at a European level in 2003/2004. Class labelling for a risk of suicide and related thoughts and behaviours was adopted for all the SSRIs based on data reviewed in 2004.

As stated before, class labelling for a risk of suicide and related thoughts and behaviours was adopted for all the Selective Serotonine Reuptake inhibitors (SSRIs) based on data reviewed in 2004. Paroxetine is an SSRI. Suicidal ideation and behaviour is already addressed in the Paroxetine Summary of Product Characteristic (SmPC).

Best wishes,

RosalindClinical Trials UnitMHRA

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So, there you have it, folks. The MHRA decided to highlight the increased risk of suicide among consumers under age 24, and they decided not to highlight the increased risk of suicide among consumers over 24.

Why didn't the MHRA feel the need to highlight the 22 adult deaths that occurred in the Paxil trials? It appears the MHRA believes Paxil isn't safe for children, but is safe for adults?

Why, in 2017, is the MHRA still not updating the Paxil warning label for adults?

Why do the MHRA continue to highlight the risk of patients under the age of 24?

I think I know why. GSK already knew that their ideal target market for Paxil was not going to be children. GSK is not allowed to promote Paxil to children (but they still did and were fined for their criminal behavior.)

But GSK was not about to lose Paxil profits when it came to capturing the adult market. MHRA helped them out by emphasizing in the patient information leaflet that the risk is only for consumers under 24. By intentionally printing these specific words, "young adults," in bold face type, MHRA is essentially telling older consumers: "Pay no attention to this increased suicide warning if you are over 24. This product poses no increased risk of death."

Obviously, MHRA should warn older adults by highlighting the 22 deaths and including older adults in the warning. Perhaps MHRA's CEO, Ian Hudson, doesn't want to do this because, whilst under oath in 2000, he stated he had seen no evidence to suggest that Paxil "caused any person, worldwide, to commit an act of homicide or suicide."

I'll leave the final words to Ian Hudson,um, Mayor Vaughn who, despite knowing about the risks created by keeping the Amity beaches open, had this to say...